HIV dementia in clade B occurs in up to 27% of patients with advanced HIV prior to effective treatment and has been associated with CNS white matter disease, often affecting speed of processing and motor functioning. [1
]. We have previously reported a cross sectional HIV dementia rate of 31% in this same group from Uganda presumably with subtype A and D [22
Here, we assessed performance between HIV seronegative controls and HIV seropositives in Uganda where HIV clades D and A predominate over clade B [14
]. Variations in HIV clade could lead to differences in prevalence rates, and/or differences in the functional deficit pattern of HIV Dementia. Increased neurotropism relative to clade B would lead to a higher prevalence of AIDS Dementia in non B clade endemic areas, while decreased neurotropism would result in lower prevalence rates. Similarly, differences in the underlying neuropathological areas affected across clades would result in changes in the pattern of neurological and neuropsychological functional impairments. For example, a greater preference for frontal areas in one clade, could result in larger deficits in executive functioning for those affected. Our primary objective was to characterize the pattern of neuropsychological functioning in this Ugandan cohort.
In Uganda, a setting of predominantly HIV clade D and A in sub-Saharan Africa, our study found significant group differences between the HIV seronegatives and HIV seropositives on measures of verbal learning and memory, speed of processing, attention and executive functioning. As HIV disease stage progressed, correlations with poorer verbal learning and memory, speed of processing, attention/working memory, and executive function were found. Characterization of neuropsychological performance across MSK AIDS Dementia Stage found that all tests were poorer in those with MSK AIDS Dementia compared to those without. Executive function, Speed of processing, and Gross Motor functioning were poorer in those with MSK Subclinical Dementia than those HIV+ individuals with no evidence of dementia.
HIV+ Ugandans demonstrated a relative decline, in measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. This is a similar pattern to what has been found in the US, Europe and Australian settings, and would suggest that the pattern of neuropsychological loss will be the same with clade A and D HIV infection [5
]. In turn, this would suggest that HIV clade A and D have the same underlying pattern of neuropathology. There was no formal assessment of clade in this study. However, another study found faster systemic progression in clade D over clade A in Uganda. [23
] Given that neuropsychological deficits are often correlated to immunological deficits and systemic disease progression, one would expect higher deficits in those with clade D compared to clade A over time.
We found no significant difference in the fine and gross motor tests between the HIV positive and HIV negative groups in this setting. However, in this study we found that both fine and gross motor performance become more impaired in those with AIDS Dementia, and may be useful in separating those with Subclinical Dementia from normals. In a separate study using the International HIV Dementia Scale, (IHDS), a screening test for HIV dementia which evaluates motor and psychomotor speed performance, we have found that motor functioning remains important in determining AIDS Dementia Stage in these Ugandan patients [24
]. Another study on cognitive functioning in a non-clade B HIV sample has suggested that other HIV clades are neuropathogenic. Cognitive functioning in individuals infected with clade C in India found neuropsychological deficits in HIV+ subjects compared to HIV- subjects [25
AIDS related neurological disease has a very high cost in terms of loss of functional ability. Patients have higher rates of unemployment, decreased ability to perform their activities of daily living including difficulty completing such tasks as meal preparation and housework [8
]. These data suggest that Ugandan patients demonstrate a relative decline on measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. These deficits are likely to have an impact on a patient's ability to maintain employment outside of the home, or to complete activities to maintain the household. When this happens, many others are affected as well. Dependent children or parents will also experience the losses associated with these deficits: less income, food and caretaking ability. Initiation of antiretroviral therapy in these individuals may reverse some of these neuropsychological deficits, and allow continued employment and household maintenance.
There are noteworthy limitations that should be considered when interpreting the current study's findings. While there is a need for neurocognitive assessments in resource limited settings, our battery was relatively brief, which may limit its sensitivity to HIV-related neurocognitive impairment [27
]. Further, we suspect that speaking Luganda is a surrogate marker for multiple factors, such as lower socioeconomic status, decreased access to healthcare and decreased nutritional status. These factors were not measured in the current study, but inclusion of these factors in future work may determine any association with an increased risk of HIV dementia. Control subjects were determined by requiring the negative control subjects to have a negative HIV ELISA in the last year. There is a chance that some control subjects could have become HIV positive within that time frame.
Further studies to characterize HIV associated dementia and neuropsychological functioning in resource limited settings are necessary. The response of neurological disease to treatment will also be important to characterize. These studies will be particularly difficult to engage in, but can be aided by committed researchers on the ground that are competent and bring the necessary local experience to successfully complete them.